Cellular/Molecular

Hypothalamic gonadotropin releasing-hormone (GnRH) neurons, which regulate sexual reproduction, integrate inputs from different sources along single, rarely branched dendrites. Dendritic integration generally depends on the expression and distribution of neurotransmitter receptors and voltage-sensitive ion channels. In GnRH neurons, these include GABAA receptors, whose activation depolarizes the neurons, and L-type Ca2+ channels, which are activated upon GABA-induced depolarization. Hemond et al. found that activation of L-type channels was required for GABAergic stimulation to induce spiking in mouse hypothalamus slices. Some neurons did not appear to express L-type Ca2+ channels, which may have accounted for a similar proportion of neurons that did not respond to GABAergic stimulation. When present, L-type channels were distributed biphasically along dendrites, with high concentrations at proximal and distal ends and low concentrations between. In contrast, GABAA receptor density decreased with distance from the soma. Because of this arrangement, spiking was induced only when proximal dendrites were stimulated with GABA.

Development/Plasticity/Repair

New neurons are generated in the subventricular zone (SVZ) throughout adulthood. These neurons migrate along the rostral migratory stream to the olfactory bulb, where they differentiate into GABAergic granule cells, form synapses with glutamatergic tufted and mitral cells, and thus become incorporated into existing circuits. GABA regulates proliferation of neural stem cells in the SVZ, migration of neuroblasts, and as now reported by Pallotto et al., maturation of neurons in the olfactory bulb. Removing the α2 subunit of GABAA receptors (GABAARs) from newborn neurons not only reduced the amplitude of evoked IPSCs in these cells, but also reduced the length, branching, and spine density of maturing neurons' dendrites. As newborn granule cells mature, they normally exhibit exuberant dendritic growth followed by pruning; this did not occur in neurons lacking α2-GABAARs. Furthermore, whereas glutamatergic synapses form on dendritic shafts and subsequently move to spines in wild-type neurons, these synapses persisted on shafts in neurons lacking α2-GABAARs.

Behavioral/Systems/Cognitive

People speak 130–190 words per minute (wpm), but they can understand speech accelerated to ∼400 wpm. Nonverbal auditory stimuli presented at higher rates can be distinguished, suggesting a comprehension bottleneck occurs in language centers. Vagharchakian et al. used functional imaging to identify brain areas whose activity depended on presentation rate and intelligibility of 12-word sentences. Sentences compressed to 40% of their original duration were difficult to understand, and those compressed to 20% were incomprehensible. Whereas the amplitude and duration of activation in primary auditory cortex increased linearly with stimulus duration, activity in left inferior frontal gyrus and superior temporal sulcus—including perisylvian language areas—was similar for all intelligible sentences and decreased sharply at 20% compression. Activation in anterior insula/inferior frontal areas was greatest at 40% compression. The authors propose that these latter regions store words delivered faster than they can be comprehended, and that comprehension collapses when this buffer is overloaded.

Neurobiology of Disease

Although Alzheimer's disease (AD) is characterized by accumulation of β-amyloid (Aβ) in extracellular plaques, the amount of soluble Aβ—rather than its deposition—is correlated with cognitive decline. Aβ is neurotoxic, and Aβ produced by one set of neurons can induce pathology in neighboring neurons. How neuronal dysfunction develops in AD and the extent to which intracellular and extracellular Aβ oligomers are involved remain poorly understood, however. Nath et al. now demonstrate that pathology can spread from cell to cell by direct transfer of soluble Aβ oligomers. Fluorescently labeled Aβ oligomers injected into individual neurons in rat hippocampal cultures diffused throughout the cell, then aggregated in granules that spread to surrounding glia and neurons. When Aβ-expressing cells were added to untreated “acceptor” cultures, Aβ was transferred to some acceptor neurons. Within days, these acceptor cells showed signs of cytotoxicity, while cells that did not acquire Aβ remained healthy.